Ovarian hormones and chronic administration during adolescence modify the discriminative stimulus effects of delta-9-tetrahydrocannabinol (Δ⁹-THC) in adult female rats.
Ovarian hormones and chronic administration during adolescence modify the discriminative stimulus effects of delta-9-tetrahydrocannabinol (Δ⁹-THC) in adult female rats.
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DOI：
10.1016/j.pbb.2012.06.008
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发表时间：
2012-09
影响因子：
3.6
通讯作者：
Sutton, Jessie L.
中科院分区：
文献类型：
--
作者：
Winsauer, Peter J.;Filipeanu, Catalin M.;Bailey, Evangeline M.;Hulst, Jerielle L.;Sutton, Jessie L.
关键词：
在青春期滥用大麻可能会改变其在成年期的滥用倾向，通过改变产生的内感受性（歧视性）刺激，特别是在女性中，由于与卵巢激素的相互作用。为了检验这种可能性，在青春期，雌性雌性大鼠（性腺完整或卵巢切除（OVX））每天接受40次腹腔注射生理盐水或5.6 mg/kg Δ9-THC，分为4个实验组（完整/生理盐水、完整/Δ9-THC、OVX/生理盐水和OVX/Δ9-THC）。然后训练这些组在固定比例（FR） 20的食物呈现时间表下区分Δ9-THC （0.32-3.2 mg/kg）和生理盐水。在为每组受试者建立训练剂量后，用不同剂量的Δ9-THC代替训练剂量，得到药物杠杆反应和反应率的剂量效应（概化）曲线。结果表明：1)在对照条件下，OVX/生理盐水组的平均应答率明显高于其他三组；2)在Δ9-THC剂量低于训练剂量时，OVX/生理盐水组的thc水平应答百分比均高于对照组；3)OVX/Δ9-THC组对Δ9-THC降率作用的敏感性明显低于其他组。此外，western blot分析显示，OVX和完整雌性的慢性Δ9-THC降低了纹状体中大麻素1型受体（CB1R）的水平，降低了海马中环腺苷单磷酸反应元件结合蛋白（p-CREB）的磷酸化。与海马相比，慢性Δ9-THC只降低了OVX组纹状体的p-CREB。细胞外信号调节激酶（ERK）不受激素状态或慢性Δ9-THC的显著影响。总之，这些雌性大鼠的数据表明，青春期人类女性滥用大麻素可能会改变她们成年后对大麻素的反应，并对大脑发育产生严重后果。
Marijuana abuse during adolescence may alter its abuse liability during adulthood by modifying the interoceptive (discriminative) stimuli produced, especially in females due to an interaction with ovarian hormones. To examine this possibility, either gonadally intact or ovariectomized (OVX) female rats received 40 intraperitoneal injections of saline or 5.6 mg/kg of Δ9-THC daily during adolescence, yielding 4 experimental groups (intact/saline, intact/Δ9-THC, OVX/saline, and OVX/Δ9-THC). These groups were then trained to discriminate Δ9-THC (0.32–3.2 mg/kg) from saline under a fixed-ratio (FR) 20 schedule of food presentation. After a training dose was established for the subjects in each group, varying doses of Δ9-THC were substituted for the training dose to obtain dose-effect (generalization) curves for drug-lever responding and response rate. The results showed that: 1) the OVX/saline group had a substantially higher mean response rate under control conditions than the other three groups, 2) both OVX groups had higher percentages of THC-lever responding than the intact groups at doses of Δ9-THC lower than the training dose, and 3) the OVX/Δ9-THC group was significantly less sensitive to the rate-decreasing effects of Δ9-THC compared to other groups. Furthermore, at sacrifice, western blot analyses indicated that chronic Δ9-THC in OVX and intact females decreased cannabinoid type-1 receptor (CB1R) levels in striatum, and decreased phosphorylation of cyclic adenosine monophosphate response element binding protein (p-CREB) in intact and OVX females in hippocampus. In contrast to hippocampus, chronic Δ9-THC only decreased p-CREB in the OVX group in striatum. Extracellular signal-regulated kinase (ERK) was not significantly affected by either hormone status or chronic Δ9-THC. In summary, these data in female rats suggest that cannabinoid abuse by adolescent human females could alter their subsequent responsiveness to cannabinoids as adults and have serious consequences for brain development.
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DOI：
10.1007/bf00421388
发表时间：
1976-01-01
期刊：
PSYCHOPHARMACOLOGIA
影响因子：
--
作者：
COLPAERT, FC;NIEMEGEERS, CJE;JANSSEN, PAJ
通讯作者：
JANSSEN, PAJ
影响因子：
1.9
作者：
Daniel, JM;Winsauer, PJ;Moerschbaecher, JM
通讯作者：
Moerschbaecher, JM
影响因子：
3.4
作者：
Lichtman, AH;Martin, BR
通讯作者：
Martin, BR
影响因子：
3.4
作者：
LICHTMAN, AH;DIMEN, KR;MARTIN, BR
通讯作者：
MARTIN, BR
DOI：
10.1006/bbrc.2000.2406
发表时间：
2000-04-02
影响因子：
3.1
作者：
González, S;Bisogno, T;Fernández-Ruiz, JJ
通讯作者：
Fernández-Ruiz, JJ